Introduction. Individuals acutely exposed to ionizing radiation demonstrated an increased risk of incidence of malignant neoplasms of the hematopoietic and lymphoid tissues (HLTT). Meanwhile papers describing the impact of chronic radiation exposure on the hematopoietic system are sparse.
Aim — to assess incidence and mortality rates for HLTT in a cohort of workers exposed to chronic, occupational ionizing radiation.
   Materials and methods. Incidence and mortality rates of HLTT were assessed for workers of a nuclear industrial enterprise who had been hired at the facility from 1948–1982 and followed up until the end of 2018 (22,377 workers). All workers of the study cohort were externally and/or internally exposed to ionizing radiation during occupational industrial activities. In the studied cohort of workers, 186 cases and 123 deaths (as a main cause) from HLTT were registered throughout the entire follow-up period (1948–2018).
   Results. Crude incidence and mortality rates of HLTT in workers of the study cohort were associated with sex, attained age of workers and calendar follow-up period. Standardized incidence and mortality rates for males were significantly higher compared to females. The standardized HLTT incidence rates (per 1000 person-years of observation) were 0.36 ± 0.03 in males and 0.23 ± 0.04 in females while the standardized HLTT mortality rates were 0.16 ± 0.02 in males and 0.09 ± 0.02 in females.
   Conclusions. The study revealed significant increasing trends for incidence rates of chronic leukemia and lymphoma by the end of the follow-up period (31. 12. 2018).

   Introduction. The option of observation without therapy with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) patients is already included in Russian and international clinical guidelines. Evaluation of long-term follow-up results of treatment free remission (TFR) in CML patients is relevant for the introduction of this approach into routine clinical practice.
   Aim — to demonstrate the outcomes in a long-term follow-up of CML patients who discontinued TKI therapy in the RU-SKI trial.
   Patients and methods. The prospective study included 98 CML patients with TKI therapy duration ≥ 3 years and a deep molecular response (DMR, BCR::ABL1 ≤ 0.01 %) duration ≥ 2 years. TKI therapy was resumed with the loss of a major MR (MMR, BCR::ABL1 > 0,1 %).
   Results. Median time of follow-up after TKI discontinuation was 64 months (range of 51–86 months). Survival without MMR loss at 3 and 5 years after TKI discontinuation was 51 % (CI 41–61 %) and 46 % (CI 36–57 %) respectively. From 3 to 5 years of follow-up without therapy, the loss of MMR occurred in 2 (4 %) patients. There was no MMR loss observed after 5 years of follow-up. In patients with first and second treatment discontinuation, survival without MMR loss was 50 % versus 12,5 %
(р = 0,039). All 50 patients with molecular relapses regained MMR and MR4 after TKI therapy resumption. BCR::ABL1 level fluctuations 0,01–0,1 % were in 62 % (n = 29) patients, who were in TFR at the time of analysis. Loss of MR4 was observed in 38 (42 %) from 90 patients with first TKI discontinuation. Survival without MMR loss from MO4 loss was 24 % at 5 years after TKI discontinuation. Loss of MO4 in the first 3 months after TKI cessation was associated with a high probability of further MMR loss (8 % versus 54 % in patients with loss of MO4 for > 3 months, p = 0.00015).
   Conclusion. The low frequency of late relapses (4 % after 3 years of follow-up) and the possibility of long-term persistence of minimal residual disease (MRD) after discontinuation of therapy determine the need to optimize the timing of molecular monitoring, taking into account the MRD status of patients.

   Introduction. Over the past decade significant progress has been made in the treatment of patients with chronic myeloid leukemia (CML). In the most patients it is possible to reach a major molecular response (MMR) and maximize overall survival (OS). However, in real clinical practice in the regions of Russia, there is a number of unresolved problems that have led to the deterioration in the results of therapy such as, low patient compliance to treatment and the lack of proper control by doctors of polyclinics over the intake of medications and the course of the disease.
   Aim — to compare the incidence and results of therapy of patients with chronic myeloid leukemia in Novosibirsk and the Novosibirsk region.
   Materials and methods. The results of therapy of 333 CML patients were studied. The incidence and prevalence of disease, 5-year OS and predicted 10-year OS as well as 5-years and 10-years predicted event-free survival (EFS) have been evaluated. Results of therapy and compliance to treatment of 214 patients with CML who had been treated with imatinib for more than 18 months also were studied.
   Results. The incidence from 2004 for 2020 was 0.62 per 100,000 population per year, the prevalence of CML in Novosibirsk over the past 15 years has increased from 3.27 to 10.89 cases per 100,000 population, in the Novosibirsk region – from 1.83 to 5.55 cases per 100,000 population. Median OS was not reached. The 5-year OS and 10-year OS in Novosibirsk were 85.7 and 72.5 %, respectively. The 5-year OS and 10-year OS in Novosibirsk region was 80.5 and 72.3 %, respectively. The 5-year EFS and 10-years predicted EFS in Novosibirsk was 55.8 and 40.8 %, respectively. The 5-year EFS and 10-years predicted EFS in Novosibirsk region was 34.9 and 18.7 %, respectively (p = 0.02882). The median EFS in Novosibirsk and Novosibirsk region was 6.8 and 2.7 years, respectively. Among patients treated in Novosibirsk, 134 patients (95.7 %) achieved a complete clinical and hematological response (CHR), 124 patients (88.5 %) — a complete cytogenetic response (CCyR), 95 patients (67.8 %) achieved MMR. Treatment failure was in 45 patients who did not obtain MMR and 16 (35.5 %) of 45 did not achieve even CCyR. The 2^nd generation tyrosine kinase inhibitors (TKI 2) were administered to 18 patients who were resistant to imatinib. CHR was maintained in 17 out of 18 patients (94.4 %), CCyR — in 14 patients (77.7 %), MMR was achieved in 12 patients (66.7 %). In Novosibirsk region CHR was obtained in 72 of 74 patients (97.3 %), CCyR — in 50 patients (67.6 %), MMR — in 13 patients (17.6 %). No MMR was achieved in 61 patients (82.4 %), 17 (22.9 %) of them failed to obtain even CCyR. TKI 2 were administered to 7 out of these 61 patients, and 6 (85.7 %) of 7 maintained CHR, 5 patients (71.4 %) — CCyR, 1 patient (14.3 %) – MMR. Adherence to imatinib therapy was significantly lower in the group of patients with therapy failure than in patients with an optimal response both in Novosibirsk (p < 0.00001) and in Novosibirsk region (р = 0,000002).
   Conclusion. We have revealed a significant increase in the incidence of CML in Novosibirsk and Novosibirsk region. The problems in treatment are as follows: insufficient control by primary care physicians over patients living in Novosibirsk region and low treatment compliance of patients.

   Introduction. Assessment of the state of the hemostasis system in cardioanesthesiology is carried out both clinically and using standard laboratory tests — thromboelastography (TEG), rotational thromboelastometry (ROTEM), or a combination of both. Both TEG and ROTEM are designed to detect disorders in the hemostasis system in real time.
   Aim – to evaluate the informativeness of ROTEM performed at the stage of cardiopulmonary bypass (CPB) before neutralization of heparin with protamine and to study the prognostic value of this study in assessing the risk of postoperative bleeding during cardiac surgery with a high risk of bleeding.
   Materials and methods. The assessment of the diagnostic significance of ROTEM studies at the CPB stage is based on the observation of 31 patients operated on from July to October 2018. The median age of these patients was 55 years (31–72 years). The criteria for inclusion of patients in the study were the performance of planned cardiac surgery with a high risk of bleeding: operations on the aorta, combined operations (coronary bypass surgery and/or surgery on the valve(s), multivalve correction), including repeated. Methods of descriptive statistics, correlation and comparative analyses, and ROC-analysis were used to assess the diagnostic and prognostic capabilities of ROTEM research during CPB against the back=-ground of high doses of heparin.
   Results. A statistically significant linear correlation was noted between A5 and MCF indicators in EXTEM, FIBTEM and PLTEM tests performed both during and after CPB. The results obtained indicate that determining the cause of bleeding and deciding on the choice of therapy is possible significantly earlier than the MCF indicator is determined, namely 5 minutes after the start of blood clotting in the ROTEM study. The informative value of ROTEM studies performed during CPB is shown, however, when interpreting the results, it is necessary to focus not only on the reference intervals, but also on the obtained cut-off levels for ROTEM parameters during CPB for early detection of hypofibrinogenemia or thrombocytopenia after CPB.
   Conclusion. ROTEM performed with the use of high doses of heparin during CPB is informative for the choice of pathogenetically justified therapy for possible bleeding.

   Introduction. Along with the quantitative characteristics of the von Willebrand factor (vWF), more attention is paid to its qualitative characteristics in patients with von Willebrand disease (vWD).
   Aim — to evaluate the frequency of vWF binding capacity disorders with type I collagen (vWF:CBAI) and type III collagen (vWF:CBAIII) in patients diagnosed with type 1 vWD and the diagnostic capabilities of these tests.
   Material and methods. The prospective study included 224 female patients with previously diagnosed vWD type 1. The following tests were performed in the venous blood sample: von Willebrand factor antigen (vWF:Ag), vWF:CBAI, vWF:CBAIII. The control group consisted of 80 healthy female blood donors.
   Results. In the control group, the values of vWF:CBAI and vWF:CBAIII did not exceed the reference intervals. A decrease in vWF:CBAI was detected in 133 (59.4 %) patients and vWF:CBAIII in 26 (11.6 %) patients. An isolated decrease in vWF:CBAI was detected in 87 (38.8 %) patients . An isolated decrease in vWF:CBAIII was less common — in 6 (2.7 %) patients.
   Conclusion. The study of vWF:CBAI and vWF:CBAIII appears to be useful as an additional diagnostic test to improve the distinction between healthy individuals and those with VWD.

   Introduction. The mutational status of immunoglobulin heavy chain variable region genes (IGHV) is the most important prognostic factor in chronic lymphocytic leukemia (CLL). Furthermore, a significant narrowing of the IGHV gene repertoire is found in CLL and other lymphoproliferative diseases.
   Aim — to review the publication data on the IGHV genes repertoire and mutational status in CLL and other lymphoproliferative diseases regarding their clinical significance.
   General information. Nucleotide sequence of rearranged IGHV genes is a unique marker of a tumor clone. CLL patients with unmutated IGHV genes have an extremely unfavorable disease outcome in contrast to the patients with mutated IGHV genes. Patients with mutated IGHV genes benefit from conventional immunochemotherapy, while non-mutated IGHV patients require therapy escalation with new targeted drugs. The study of IGHV genes and stereotyped antigen receptors repertoire makes possible to identify additional groups of CLL patients with specific genetic and clinical features. Stereotype receptors are also detected in other lymphoproliferative diseases, but their clinical significance has not yet been defined. However, stereotyped receptors are found to be disease-specific.

   Introduction. Hemophilia is an X-linked hereditary blood clotting disorder caused by insufficiency of blood clotting factor VIII or IX that affects mainly men. In extremely rare cases, the disease can be observed in women, which is most often associated with asymmetric inactivation of the X chromosome. The severity of hemophilia in women does not differ from that in men.
   Aim – to present a clinical observation of surgical treatment of stage 4 hemophilic arthropathy in a woman with severe hemophilia A.
   Main findings. Female patient T., 39 years old, was admitted to the National Medical Research Center for Hematology with a preliminary diagnosis: hereditary deficiency of factor VIII. She had an extension of the APTT to 68.8 sec, a high level of Willebrand factor activity — 222 %, and the concentration of Willebrand factor antigen of 178.1 mg/l, and a decrease in the level of factor VIII to 1.6 %. According to molecular genetic analysis, intron 22 inversion associated with severe hemophilia A was detected in the F8 gene. Throughout the patient’s life, hemarthrosis of the knee, ankle and elbow joints were observed, which led to the development of severe arthropathy of varying severity. The woman underwent total knee arthroplasty and arthrolysis of the left ankle joint. The postoperative period proceeded without complications. Hemostatic replacement therapy was performed with a recombinant factor VIII.

   Introduction. Platelet dense granule disorders are a group of rare heterogeneous disorders of the blood coagulation system in which bleeding occurs due to functional and morphological disorders of platelet organelles accumulating phosphates and bioactive amines.
   Aim — to present a clinical case of a 37-year-old patient with severe hemorrhagic syndrome.
   Basic information. An observation of the occurrence of hemorrhagic manifestations of unspecified genesis in a patient is described. The results of 25 healthy volunteer examinations of both sexes were used as a control for testing methods of diagnosis of Platelet dense granule disorder. Methods of assessing the hemostasis system, platelet morphological features using electron microscopy, as well as platelet accumulation of mepacrine using a flow cytometer were studied. Platelet dense granule disorder was detected by electron microscopy and confirmed by flow cytometry in a patient with severe hemorrhagic manifestations, in whom the diagnosis was not verified for a prolonged period of time.

   Introduction. Only a massive radiation accident, and not individual incidents heterogeneous in terms of exposure conditions, contributes to the revision and development of knowledge and therapeutic capabilities in acute radiation syndrome (ARS).
   Aim — to present recommendations based on literature data and own clinical experience for the diagnosis and treatment of a typical bone marrow form of ARS from relatively uniform irradiation.
   General information. An analysis of the literature on the problem of diagnosis and treatment of ARS was carried out, and the experience of providing medical care to victims of the April 26, 1986 radiation accident at the Chernobyl Nuclear Power Plant (104 patients with OLB) in the clinical department of the A.I. Burnazyan State Medical Center of the FMBA of Russia is summarized. When admitting individuals involved in a radiation accident into a medical institution, one of the most important measures of action is to conduct medical sorting, that is, the distribution of victims into groups according to the principle of need for homogeneous therapeutic, preventive and evacuation measures, depending on medical indications, specific conditions of the situation and the prognosis of the patient's survival based on dose assessment and prediction of the severity of the course of ARS by all available methods of physical and biological dosimetry (calculation method, simulation of the situation, clinical signs of the primary reaction to radiation, cytogenetic method, absolute number of peripheral blood lymphocytes during the first 8 days after irradiation, dynamics of the absolute number of peripheral blood neutrophils, etc.). The scope of therapeutic measures depends on the severity of the developing ARS, including the therapy of infectious complications and hemorrhagic syndrome. The appointment of myelostimulation in order to reduce the depth and duration of radiation-induced cytopenia is recommended when irradiated at a dose of more than 1.5 Gy. Transplantation of allogeneic hematopoietic stem cells in ARS is recommended in a narrow dose range from 10 to 13 Gy in the absence of concomitant severe injuries and burns. Recommendations for the treatment of oropharyngeal and intestinal syndromes are given.

   Introduction. Currently, there is no unequivocal opinion on the optimal list of studies for the genetic diagnosis of oncohematological disorders in children and adults. These discrepancies are due to the limited technological capabilities of laboratories, the rapid development of science, and a significant expansion of the range of new molecular markers, that are attractive, but only for a limited group of patients. Moreover, in modern conditions of limited access to resources, it seems important to bring desires, interests and opportunities to a common denominator.
   Aim — to develop unified approaches to the cytogenetic and molecular genetic diagnosis of oncohematological diseases in children and adults based on the consensus opinion of the panel of experts.
   Main findings. The review proposes the arrangement of cytogenetic and molecular genetic diagnostic tests in oncohematological disorders in children and adults into 3 categories depending on the frequency of genetic aberrations, the study complexity and the prognostic impact. Based on this and taking into account the diagnosis and age of patients, the minimal and optimal lists of clinically significant parameters and research markers were identified. The basic preanalytical principles for conducting cytogenetic and molecular genetic studies in oncohematology are pointed out. A brief description of a conventional cytogenetic study and a polymerase chain reaction for the diagnosis of oncohematological diseases is given. The paper also focused on the need for reference diagnostics of cytogenetic and molecular genetic studies in oncohematology. The article is addressed to the specialists in the field of laboratory genetics, clinical laboratory diagnostics, but may also be of interest to hematologists, pediatric oncologists and doctors of related branches.